7W7E: PDB entry 7W7E

Cryo-EM structure of the alpha2A adrenergic receptor GoA signaling complex bound to a biased agonist. Determined by electron microscopy at 3.4 Å resolution. Released 28 Sept 2022.

Method: Electron microscopy
Resolution: 3.4 Å
Organisms: Homo sapiens, Mus musculus
Chains: 5
Atoms: 8,524
Mol. weight: 170.15 kDa
Ligands: W58
Released: 28 Sept 2022

Explore 7W7E in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

7W7E contains 25 α-helices and 65 β-strands across 5 chains. Residue ranges use author residue numbering, as in the PDB file, from PDBe. To see them in 3D, choose the Cartoon representation with Secondary structure coloring: helices, sheets and coils get different colors.

Chain A: 6 helices, 10 β-strands

Element	Residues	Length	Sheet
α-helix	7-28	22
β-strand	34-38	5	1
α-helix	47-53	7
β-strand	186-188	3	1
β-strand	191-192	2	2
β-strand	195-196	2	2
β-strand	197-201	5	1
α-helix	213-216	4
β-strand	222-225	4	1
α-helix	243-254	12
β-strand	265-268	4	1
α-helix	297-310	14
β-strand	319-320	2	1
α-helix	330-347	18
β-strand	350	1	3
β-strand	352	1	3

Chain B: 2 helices, 32 β-strands

Element	Residues	Length	Sheet
α-helix	7-24	18
β-strand	49-51	3	4
β-strand	58-63	6	5
β-strand	69-74	6	5
β-strand	78-83	6	5
β-strand	88-94	7	5
β-strand	112-114	3	6
β-strand	121-125	5	6
β-strand	134-139	6	6
β-strand	146-151	6	7
β-strand	157-161	5	7
β-strand	166	1	7
β-strand	169-170	2	8
β-strand	175-176	2	8
β-strand	180	1	7
β-strand	190-192	3	9
β-strand	199-201	3	9
β-strand	208-210	3	9
β-strand	220-222	3	9
β-strand	232	1	10
α-helix	234-235	2
β-strand	243	1	10
β-strand	251	1	10
β-strand	253-254	2	11
β-strand	259-260	2	11
β-strand	273-278	6	12
β-strand	284-289	6	12
β-strand	294	1	13
β-strand	295-298	4	12
β-strand	304	1	12
β-strand	308	1	13
β-strand	315-320	6	4
β-strand	327-331	5	4
β-strand	335-339	5	4

Chain G: 3 helices, 0 β-strands

Element	Residues	Length
α-helix	10-23	14
α-helix	30-43	14
α-helix	53-55	3

Chain H: 3 helices, 23 β-strands

Element	Residues	Length	Sheet
β-strand	4-6	3	14
β-strand	11	1	15
β-strand	17-24	8	14
α-helix	29-31	3
β-strand	33	1	16
β-strand	34-37	4	17
β-strand	47-51	5	17
β-strand	60	1	17
β-strand	69-73	5	14
α-helix	74-76	3
β-strand	78-84	7	14
α-helix	88-90	3
β-strand	92-94	3	18
β-strand	95-96	2	17
β-strand	99	1	16
β-strand	115-117	3	18
β-strand	118	1	15
β-strand	129	1	19
β-strand	148	1	19
β-strand	162-167	6	20
β-strand	174-178	5	20
β-strand	182-183	2	20
β-strand	193-195	3	21
β-strand	200-202	3	21
β-strand	214-219	6	20
β-strand	231	1	20

Chain R: 11 helices, 0 β-strands

Element	Residues	Length
α-helix	46-75	30
α-helix	85-110	26
α-helix	122-151	30
α-helix	153-157	5
α-helix	162-180	19
α-helix	209-216	8
α-helix	217-221	5
α-helix	222-241	20
α-helix	380-414	35
α-helix	422-442	21
α-helix	446-456	11

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Guanine nucleotide-binding protein G(o) subunit alpha	A	protein	354	Homo sapiens	P09471 (AlphaFold model)
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1	B	protein	349	Homo sapiens	P62873 (AlphaFold model)
Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2	G	protein	71	Homo sapiens	P59768 (AlphaFold model)
scFv	H	protein	307	Mus musculus
Alpha-2A adrenergic receptor	R	protein	465	Homo sapiens	P08913 (AlphaFold model)

Sequence of entity 1 (A), FASTA

>7W7E_1 Guanine nucleotide-binding protein G(o) subunit alpha (chains A)
MGCTLSAEERAALERSKAIEKNLKEDGISAAKDVKLLLLGAGESGKSTIVKQMKIIHEDG
FSGEDVKQYKPVVYSNTIQSLAAIVRAMDTLGIEYGDKERKADAKMVCDVVSRMEDTEPF
SAELLSAMMRLWGDSGIQECFNRSREYQLNDSAKYYLDSLDRIGAADYQPTEQDILRTRV
KTTGIVETHFTFKNLHFRLFDVGGQRSERKKWIHCFEDVTAIIFCVALSGYDQVLHEDET
TNRMHESLMLFDSICNNKFFIDTSIILFLNKKDLFGEKIKKSPLTICFPEYTGPNTYEDA
AAYIQAQFESKNRSPNKEIYCHMTCATDTNNIQVVFDAVTDIIIANNLRGCGLY

Sequence of entity 2 (B), FASTA

>7W7E_2 Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 (chains B)
HHHHHHGSSGSELDQLRQEAEQLKNQIRDARKACADATLSQITNNIDPVGRIQMRTRRTL
RGHLAKIYAMHWGTDSRLLVSASQDGKLIIWDSYTTNKVHAIPLRSSWVMTCAYAPSGNY
VACGGLDNICSIYNLKTREGNVRVSRELAGHTGYLSCCRFLDDNQIVTSSGDTTCALWDI
ETGQQTTTFTGHTGDVMSLSLAPDTRLFVSGACDASAKLWDVREGMCRQTFTGHESDINA
ICFFPNGNAFATGSDDATCRLFDLRADQELMTYSHDNIICGITSVSFSKSGRLLLAGYDD
FNCNVWDALKADRAGVLAGHDNRVSCLGVTDDGMAVATGSWDSFLKIWN

Sequence of entity 3 (G), FASTA

>7W7E_3 Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 (chains G)
MASNNTASIAQARKLVEQLKMEANIDRIKVSKAAADLMAYCEAHAKEDPLLTPVPASENP
FREKKFFCAIL

Sequence of entity 4 (H), FASTA

>7W7E_4 scFv (chains H)
MLLVNQSHQGFNKEHTSKMVSAIVLYVLLAAAAHSAFADVQLVESGGGLVQPGGSRKLSC
SASGFAFSSFGMHWVRQAPEKGLEWVAYISSGSGTIYYADTVKGRFTISRDDPKNTLFLQ
MTSLRSEDTAMYYCVRSIYYYGSSPFDFWGQGTTLTVSSGGGGSGGGGSGGGGSDIVMTQ
ATSSVPVTPGESVSISCRSSKSLLHSNGNTYLYWFLQRPGQSPQLLIYRMSNLASGVPDR
FSGSGSGTAFTLTISRLEAEDVGVYYCMQHLEYPLTFGAGTKLELKGSLEVLFQGPAAAH
HHHHHHH

Sequence of entity 5 (R), FASTA

>7W7E_5 Alpha-2A adrenergic receptor (chains R)
MFRQEQPLAEGSFAPMGSLQPDAGNASWNGTEAPGGGARATPYSLQVTLTLVCLAGLLML
LTVFGNVLVIIAVFTSRALKAPQNLFLVSLASADILVATLVIPFSLANEVMGYWYFGKAW
CEIYLALDVLFCTSSIVHLCAISLDRYWSITQAIEYNLKRTPRRIKAIIITVWVISAVIS
FPPLISIEKKGGGGGPQPAEPRCEINDQKWYVISSCIGSFFAPCLIMILVYVRIYQIAKR
RTRVPPSRRGPDAVAAPPGGTERRPNGLGPERSAGPGGAEAEPLPTQLNGAPGEPAPAGP
RDTDALDLEESSSSDHAERPPGPRRPERGPRGKGKARASQVKPGDSLPRRGPGATGIGTP
AAGPGEERVGAAKASRWRGRQNREKRFTFVLAVVIGVFVVCWFPFFFTYTLTAVGCSVPR
TLFKFFFWFGYCNSSLNPVIYTIFNHDFRRAFKKILCRGDRKRIV

Ligands and cofactors

ID	Name	Formula	Copies
W58	5-(3-bicyclo[4.2.0]octa-1,3,5-trienyl)-1,2,3,6-tetrahydropyridine	C13 H15 N	1

Primary citation

Structure-based discovery of nonopioid analgesics acting through the alpha 2A -adrenergic receptor. Fink, E.A., Xu, J., Hubner, H. et al. Science (2022) 377:eabn7065-eabn7065. DOI 10.1126/science.abn7065 · PubMed

Other PDB entries of the same protein (UniProt P09471 (AlphaFold model), which also has an AlphaFold model), best resolution first:

9BSB 2.32 Å, Global reconstruction of DRD2 bound to LSD in complex with a mini-GoA and scFv16…
9VJE 2.47 Å, Cryo-EM structure of 5-HT1AR-GoA in complex with buspirone
9K20 2.65 Å, Cryo-EM structure of ATP-bound P2Y purinoceptor 2-miniGo-scFv16 complex
9VJ5 2.69 Å, Cryo-EM structure of 5-HT1AR-GoA in complex with gepirone
8E9X 2.7 Å, CryoEM structure of miniGo-coupled hM4Di in complex with DCZ
9T88 2.74 Å, Cryo-EM structure of ESG-2-37-bound D3 dopamine receptor with mini-Go
9VNF 2.74 Å, Cryo-EM structure of 5-HT1AR-GoA in complex with (S)-pindolol
8YN7 2.77 Å, Cryo-EM structure of histamine H3 receptor in complex with immethridine and miniGo
8YN8 2.77 Å, Cryo-EM structure of histamine H3 receptor in complex with proxyfan and miniGo
9KVP 2.79 Å, Structure of SB290157 bound to human C3aR in complex with Go (Full map)
7W2Z 2.8 Å, Cryo-EM structure of the ghrelin-bound human ghrelin receptor-Go complex
8XXH 2.8 Å, Structure of CXCR2 bound to CXCL2 (CXCR2-CXCL2-Go Full map)

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